ABSTRACT Reproductive health decisions for women with sickle cell anemia (SCA) a congenital hemolytic anemia that causes multi-organ injury and early death, are limited by a lack of data to inform contraception choices, pregnancy management or fertility risks. In SCA, the ovaries may be injured by oxidative and hypoxic-ischemic injury. Hydroxyurea (HU), a medication used to treat SCA as early as 9 months of age, may affect fertility negatively. In a study evaluating ovarian reserve in girls with SCA treated with HU, 8 of 33 HU-treated subjects had diminished ovarian reserve, which was associated with older age and longer duration of HU use. This data supports that ovarian reserve is compromised in some patients, but the contributions of SCA, SCA complications or SCA treatments are unknown. To optimize SCA patient care and to better understand this reproductive biology, carefully designed studies of ovarian reserve that assess disease phenotype and treatment are needed. The goal of this research is to conduct a methodologically rigorous evaluation of ovarian reserve in women with SCA to assess whether SCA or its treatments are associated with diminished ovarian reserve. This evidence will help clinicians manage patients considering the risks of untreated SCA against the known and theorized risks of SCA therapies. The proposed study will investigate whether clinical features of SCA or its primary treatment, hydroxyurea, are associated with ovarian reserve in SCA by conducting (1) a cross-sectional study that entails primary data collection of measures of ovarian reserve in women with SCA and matched controls, and (2) a study of whether HU treatment, clinical and laboratory biomarkers of SCA are associated with reduced ovarian reserve. As this information will be incorporated into patient-centered decision making, we will also (3) explore patient knowledge, experiences and preferences about fertility and SCA therapies. This research, critical for understanding the effects of SCA and HU on ovarian reserve in women with SCA, will develop the principal investigator through advanced training in epidemiology and biostatistics, qualitative research methods and reproductive medicine and SCA. Few hematologists have this kind of expertise and the principal investigator will be poised to build an independent research program at the forefront of reproductive health in SCA.